GDNF-induced neurite formation was stimulated by protein kinase inhibitors and suppressed by Ras inhibitors.
The effects of various inhibitors on the glial cell line-derived neurotrophic factor (GDNF)-induced neurite formation in TGW human neuroblastoma cells were investigated. Treatment of cells with Ser/Thr protein kinase inhibitors such as staurosporine, H-7, H-8 and HA-1004, induced neurite formation without GDNF. On the other hand, tyrosine kinase inhibitors such as erbstatin, genistein and herbimycin A did not produce neurites per se, but effectively enhanced the GDNF-induced neurite formation. A phosphatase inhibitor, okadaic acid, and Ras inhibitors such as oxanosine, damnacanthal and conophylline strongly suppressed the effect of GDNF. These results suggest that a tyrosine protein kinase has a suppressive role in the neurite formation induced by GDNF and that Ras is necessary for the signaling initiated by GDNF.
Hiwasa
T
T
Department of Biochemistry, School of Medicine, Chiba University, Japan. hiwasa@med.m.chiba-u.ac.jp
Kondo
K
K
Hishiki
T
T
Koshizawa
S
S
Umezawa
K
K
Nakagawara
A
A
D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects*; D009447:Neuroblastoma; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D011090:Polyenes / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D047428:Protein Kinase Inhibitors; D016283:Proto-Oncogene Proteins p21(ras) / Q000037:antagonists & inhibitors; D019311:Staurosporine / Q000008:administration & dosage / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D011090:Polyenes; D053284:Polyunsaturated Alkamides; D047428:Protein Kinase Inhibitors; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D019311:Staurosporine; C054474:manumycin